# Calcium imaging-based insights and guidance of deep brain stimulation to enhance chronic, post-stroke rehabilitation in a rodent model of ischemia

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $633,683

## Abstract

Project Summary
Current post-stroke rehabilitation treatments assist only ~50% of patients, resulting in an urgent need to develop
new therapies for the millions of individuals who suffer from chronic motor deficits. A recently-completed Phase
I clinical trial led by our team (EDEN), showed promising results for a new deep brain stimulation (DBS)
rehabilitation treatment, with some heterogeneity in recovery outcomes across patients. To answer why some
patients respond to the treatment while others don’t, a better mechanistic understanding of how DBS contributes
to post-stroke rehabilitation is essential. Our central hypothesis is that patient-specific customization of DBS
parameters such as amplitude, frequency and duration are required to address unique differences in brain
conditions and to maximize the potential of this new treatment. The project’s goals are to study how
reorganization of the perilesional brain tissue after injury is promoted by DBS, and to develop a subject-specific
approach for tuning the DBS parameters to enhance recovery. For achieving our goals, we will use a rat model
of ischemia, where we can systematically vary the stroke injury parameters using the endothelin-1
vasoconstriction model and visualize the injury and the brain functional activity before and during recovery across
most of the dorsal cortex using two-photon microscopy and calcium imaging. Our long-term goal is to translate
similar interventions to patients, based on the lessons from rats. The Project rationale: This project 1) provides
a comprehensive platform for rigorous study of basic mechanisms of brain reorganization and generation of new
functional properties following ischemic injury in a preclinical animal model, 2) provides animal-specific
information on reorganization of cortical circuits during post-stroke recovery to address heterogeneity across
animals, and 3) enables direct comparison across different rehabilitation approaches. Aim 1 will determine the
contribution of different treatments to circuit reorganization and motor recovery after injury and Aim 2 will
demonstrate multi-facet optimization of subject-specific DBS parameters to enhance brain reorganization and
motor rehabilitation in middle-aged male and female rats for different injury types. Impact: The proposed project
will provide us with mechanistic understanding on the reorganization process of cortical neurons following an
ischemic stroke, and how efficient DBS treatment may promote it beyond current rehabilitation treatments. Such
knowledge will assist in optimizing new neuromodulation-based rehabilitation approaches, such as the EDEN
clinical trials, to assist patients. Moreover, the proposed quantitative assessment approach can be expanded to
comparatively assess the efficacy of other rehabilitation treatments and other stroke models in an unbiased way.
Therefore, the proposed work will promote better understanding of the cortical reorganization process during
recovery and has t...

## Key facts

- **NIH application ID:** 10979483
- **Project number:** 1R01NS134577-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** KENNETH B BAKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $633,683
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979483

## Citation

> US National Institutes of Health, RePORTER application 10979483, Calcium imaging-based insights and guidance of deep brain stimulation to enhance chronic, post-stroke rehabilitation in a rodent model of ischemia (1R01NS134577-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979483. Licensed CC0.

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